Project Summary/Abstract Over one third of the 700,000 strokes suffered annually occur in the posterior circulation, a major cause of which is atherosclerotic vertebrobasilar occlusive disease. Symptomatic vertebrobasilar disease carries a high annual stroke risk, averaging 10-15% per year. Advances in endovascular angioplasty and stenting have created new treatment options, but these interventions carry significant risks, and selection criteria for determining appropriate candidates remain uncertain. Prior to embarking on expensive large-scale randomized trials of intervention, it is necessary to define the appropriate high risk population most likely to benefit from treatment. The overall goal of this study is to define the population of patients with vertebrobasilar disease at highest risk of recurrent stroke. The results will be well poised to form the basis for future clinical trials of endovascular or surgical interventions. Preliminary retrospective data indicates that stroke risk in vertebrobasilar disease is strongly related to compromised intracranial blood flow, the extent of which can be measured noninvasively using quantitative magnetic resonance angiography (QMRA). The objective is to conduct a prospective multi-center observational study of patients with symptomatic angiographically confirmed vertebrobasilar stenosis (? 50%) or occlusion to test the hypothesis that those who demonstrate compromised blood flow are at higher stroke risk. Upon enrollment, subjects will undergo hemodynamic assessment with QMRA to assess large vessel flow, and MR perfusion to assess tissue level perfusion, in the vertebrobasilar territory. Subjects will be prospectively designated as demonstrating compromised or normal cerebral flow, based upon existing preliminary data; the results will be kept blinded from treating physicians and patients. Baseline clinical, laboratory, and epidemiological data will be systematically collected. Patients will be followed at monthly intervals for a minimum of 12 months for the primary endpoint of stroke in the vertebrobasilar territory. Project Narrative By defining the population of patients at highest risk of recurrent stroke, this study will significantly impact the selection criteria and likelihood for success of future clinical trials aimed at assessing interventions for the treatment of vertebrobasilar disease. Additionally, the ability to define a low risk population in whom the risks of expensive invasive interventions would be unnecessary will have an equally important impact from a public health, and health care cost, perspective.